Title: FIPA2 M-PI: Best/Erdei/Torgerson Project Summary Pediatric asthma in American Indian (AI) communities of the Northern Plains Region presents a serious health disparity. While many previous works carried out in minority communities – but not in AI children- looked at individual level of influences on pediatric asthma and made parents responsible for asthma control, our study will bring together a more comprehensive and realistic framework. Our novel approach will move the study from the collected data toward Tribal health policy change. The FIPA2 study is designed to leverage the previously NIMHD-funded Factors Influencing Pediatric Asthma study (U54MD008164) which successfully enrolled 324 Cheyenne River Sioux Tribal (CRST) children (age 6-17 years) in 2013-2017. That study also had a randomized educational clinical trial component (NCT 03302962) and we documented results of that work. In the FIPA2 study, we will examine the complex interplay between social, environmental and immunological response to viral respiratory infections an gap in knowledge that remains largely unknown. In this continued AI community-focused pediatric asthma study, we will test the hypothesis that AI children with asthma have alterations in immunological response to several viral respiratory infections as compared to those without asthma. We will also investigate whether social and environmental factors (SEF) significantly contribute to this disparity through stressed-induced modification of immune state. We will explore the role of viral respiratory infections (RSV, rhinovirus C, and influenza A and B) and SEF on asthma severity, including frequency of exacerbations, ER visits/hospitalizations, and use of asthma medications. Aim 1 will identify social and environmental factors (SEF) that contribute to asthma susceptibility, severity and long-term respiratory health. Participants will be enrolled at our Missouri Breaks Industries Research Inc. main office by working with Reservation communities. To achieve enrollment goals, we will also enroll in Rapid City, SD, an urban setting where AIs also located (12.4% of the city’s population). In Aim 2, we will examine the role of SEF on immunological and clinical response to viral respiratory infections (VRIs) in AI children with and without asthma. We will test our hypothesis that interactions with detailed survey measures of SEF with immunological and clinical outcomes of VRIs, including seasonality of viral responses in participants with and without asthma are the strongest and most significant predictors in our AI participants. Aim 3 will bring a comprehensive and vivid community input to this study and will benefit from our local community advisory board (CAB) that supports the study. We will rely on our own, experienced CBPR-based and bidirectional process evaluation. We will create a feasible and community-driven asthma prevention framework that will be effective and can be applied in other AI communities as well.